The purpose of this work is to clarify the mechanism of cell transformation by examining the genetic and physiological factors which affect cell transformation induced by chemicals and irradiation. With nine phorbol ester derivatives and two teleocidin derivatives, close correlation was observed between their potential to enhance carcinogen-initiated transformation, to induce early biochemical changes, and to promote carcinogen-initiated skin carcinogenesis in mice. The two phorbol ester derivatives showed weak activity in enhancing transformation in spite of their stron biochemical effects. The weak transformation-enhancing potential of these two derivatives was ascribed to the short life of their biochemical effects. The accumulated biochemical effects induced by all the promoter derivatives were closely correlated with their transformation-enhancing potencies, indicating that the continuity of the promoters' effects is essential for the fixation of enhancement of transformation. In the cell mutant which is highly sensitive to chemically induced transformation, the biochemical effects of promoters lasted longer than those in the resistant cells. Molecular studies on the differences between cell mutants are in progress.